Wednesday, April 30, 2014

A
walk down the ‘health aisle’ of your local supermarket is a powerful
demonstration of the popularity of the ‘free-from’ movement, including
gluten-free and grain-free. But in the pursuit of health by cutting out grains
many people may be missing out on a key source of fibre and actually increasing
their risk of chronic disease.

A
recent study in the US found a diet higher in whole grain foods is more likely
to be higher in fibre. While this may not seem like new news to most health
care professionals, it seems many consumers may have forgotten the importance
of these foods as a source of fibre.

The
study found a strong association between the intake of whole grain foods, such
as bread and breakfast cereal, with total dietary fibre intake for both
children and adults. Compared to those who ate no whole grain, adults who ate
at least 3 serves per day were 76 times more likely to fall into the highest
fibre intake group. The major whole grain sources included bread/rolls,
oatmeal, breakfast cereals, and popcorn. Among those with the highest whole
grain intake, whole grain breakfast cereals were the greatest contributor to
total dietary fibre.

To
help Australians boost their fibre intake it is important to remind people of
the importance of eating whole grain foods and high fibre grain foods in line
with the Australian Dietary Guidelines recommendation to enjoy grain foods each
day, choosing mostly whole grain and/or higher fibre varieties.

While
fruit and veggies are an important part of the diet and key sources of fibre, two recent study highlight the importance of cereal fibre in the diet. These studies add to the significant body of evidence that higher intakes of cereal fibre
reduce risk of a range of chronic conditions including obesity, heart disease,
diabetes and colorectal cancer.

In the first study, a meta analysis of 17 prospective cohort studies found higher cereal fibre
intakes were associated with a 23% reduced risk of type 2 diabetes. The risk
reduction from cereal fibre was stronger than both total fibre (19%) and fruit
fibre (6%). In comparison, there was no significant reduced risk with higher
fibre intakes from vegetables.

Interestingly,
this is the first study to determine the dose of fibre associated with reduced
risk of type 2 diabetes. A reduced risk was seen with as little as 3 grams of
cereal fibre per day and the risk decreased by 6 % for each additional 2 grams
per day. In comparison a threshold of 25
grams of total fibre was needed before a significant risk reduction was seen. The second study, an analysis of two large US cohort studies, found heart attack survivors with higher cereal fibre intake had a 25% lower risk of dying in the nine years following their heart attack. Cereal fibre intake in particular demonstrated the greatest protection compared to other sources of fibre.

The
current Nutrient Reference Values for dietary fibre are based on an estimated
adequate intake for gastrointestinal function and adequate laxation. However
this study adds to the significant body of evidence that higher intakes of
cereal fibre reduce risk of a range of chronic conditions including obesity,
heart disease, diabetes and colorectal cancer. Encouraging Australians to
choose foods high in cereal fibre more often and ensuring whole grain foods are
available may assist people to meet and/or exceed the adequate intakes for
dietary fibre and achieve health benefits beyond the effects of fibre on
gastrointestinal function and laxation.

Reicks M, Jonnalagadda S, Albertson AM, Joshi N. Total dietary fibre intakes in the US population are related to whole grain consumption: results from the National Health and Nutrition Examination Survey 2009 to 2010. Nutrition Research. 2014,34(3):226-234.

The avoidance of wheat- and
gluten-containing products is a worldwide phenomenon, where more thanone million Australians purchase gluten-free products for health
reasons.1 The Australian gluten-free market is growing
up to 20% annually1 and in the USA, it is suggested that
as high as 8% of the population purchase gluten- and wheat-free products.2 While coeliac disease is a well-established
entity, the evidence-base for gluten as a trigger of symptoms in patients
without coeliac disease is minimal
(so-called ‘non-coeliac gluten sensitivity’; NCGS). Gluten has been putatively linked to a wide range of conditions
including various skin problems,3 fatigue and migraine,4 weight gain5 and autism,6but most often blamed for gastrointestinal (GI) symptoms.7 Recent data has suggested NCGS may exist, however
much remains unknown and important considerations are required before diagnosis.
This update discusses the latest scientific evidence in our current understanding
of NCGS.

Background

The most well understood gluten
intolerance is coeliac disease, an autoimmune GI disease estimated to affect 1%
or more of Western populations.8 It occurs when genetically susceptible
patients are exposed to dietary gluten, the major protein in wheat, rye, barley
and related grains, activating a specific immune response. This leads to small
intestinal villous atrophy, intraepithelial lymphocytosis and the development
of GI symptoms.9 The only known treatment is a lifelong, strict
gluten-free diet (GFD).

Many of the GI symptoms seen in coeliac
disease (such as diarrhoea, abdominal pain, bloating, wind, distension
and altered bowel habit) can mimic
irritable bowel syndrome (IBS). IBS is a disorder characterised by GI
symptoms but with no abnormal pathology and affects 15% of the population.10

There is an emerging belief that gluten sensitivity
might mediate IBS symptoms.11 Until recently, there were no controlled
clinical studies investigating NCGS and the scientific evidence assessing the
effects of gluten outside of coeliac disease had focused on animal models or
cancer cell lines.12,13 Regardless, the GFD is increasingly prescribed by alternative health practitioners
and recommended on Internet sites.

Is it really gluten?

Other
components of wheat have been studied in detail, such as the carbohydrate or
more specifically, the fructan component.14Fructans are one of a group of
short-chain carbohydrates poorly absorbed in the small intestine. The poor
absorption, by virtue of their small molecular size and rapid fermentability, increases
delivery of water and fermentable substrates to the colon.15,16 These effects result in increased gas
production and GI symptoms in patients with IBS.16-18This group have been termed FODMAPs, which
stands for Fermentable Oligo-, Di-, and
Mono-saccharides And Polyols.19 A diet low inFODMAPs has become a well-understood and evidence-based
strategy, leading to symptomatic improvement in 70 to 74% of patients with IBS.17,20,21

FODMAPs
are found in a wide variety of foods and include lactose (in milk), excess fructose
(in pears, apples), fructans and fructo-oligosaccharides (FOS; in artichoke,
garlic, onions, wheat and rye), galacto-oligosaccharides (GOS; stachyose
and raffinose in legumes), and sugar polyols (sorbitol and mannitol in stone
fruits and artificial sweeteners).22,23 Recent grain and cereal composition
data has highlighted that wheat- and
rye-derived products contain the highest FODMAP content, predominantly fructans
and GOS.24 Cereal products
with the lowest FODMAP contents are mostly gluten-free, based on rice, oat,
quinoa and corn ingredients.24 Therefore, choosing ‘gluten-free’ products is likely to
result in automatically selecting a low-FODMAP diet.

What is so wrong with being gluten-free?

Exclusion of coeliac disease – The prescription of a GFD for gut and other symptoms may lead to the
under diagnosis of coeliac disease. Two in three patients with self-perceived NCGSdo not have coeliac disease adequately excluded,25whichincreases patients’
risk of inadequate management and screening of associated complications if left
untreated (i.e., reduced bone health,26 long-term mortality27).

Nutritional concerns – The GFD is markedly
restrictive, presents challenges when eating at places other than home and can
be two to three times more expensive than that of a standard diet.28 It can also be nutritionally inadequate,
especially in fiber and B-vitamins.29 In addition, at least 45% of patients with self-perceived NCGS self-initiate the GFD and have not undergone dietetic education to
ensure maintained nutritional adequacy.25 Long-term restrictive diets,
particularly avoidance of wheat- and gluten-based products, are likely
to have health implications given their important role in bowel health.

What is the current evidence behind
NCGS?

Evaluation of exclusion diets has
previously shown wheat-induced gut symptoms,30 but
given wheat is also high in fructans, such evidence for NCGS has been
inconclusive. Other studies, mostly completed in animal models31or uncontrolled clinical trials have
found some evidence for the efficacy of a GFD. In these published studies,
however, either the patients have had coeliac-associated antibodies or
intraepithelial lymphocytosis in the duodenum32,33
and, therefore, have not been convincingly defined as NCGS.

The first definitive experiment where
the effect of gluten, free from contamination from carbohydrates, was evaluated
in patients with IBS where coeliac disease had been definitively excluded was
published in 2011.34
This study was a randomised double-blind,
placebo-controlled trial of a
single dose of gluten (16 g/day for 6 wk) without a controlled background in
parallel groups (n=34). The results showed
gluten specifically induced GI
symptoms and tiredness in those who
have NCGS. Although these results were exciting, they must be reproduced to
confirm the existence of NCGS.

The same research group went onto conduct another dietary trial using a crossover design and supplying a controlled diet.35 Following a
2-week run-in period on a low FODMAP diet, 40 patients with NCGS and IBS who
were symptomatically controlled on a GFD underwent a double-blind, placebo-controlled,
randomised crossover trial of placebo, low-gluten (2g/day) or high-gluten
(16g/day) for 1 week, followed by a 2-week washout period, before crossing over
to the next diet. Protein levels were balanced with whey protein. No evidence
of specific or dose-dependent effects of gluten was observed, but FODMAP
restriction uniformly reduced residual symptoms. There were no changes in markers of potential mechanism including intestinal inflammation/injury,
immune activation or by-products of protein metabolism.

A separate gluten (16g/day) and whey (16g/day) re-challenge
in 22 of these patients showed poor reproducibility
of symptom induction to a specific protein. A very high placebo response was
found in both trials, regardless of all background dietary triggers being
controlled. Either the patients do not have NCGS as self-reported or the trial
design precluded its recognition. A
better understanding is warranted for the diagnosis of NCGS where self-reporting
is probably inaccurate.

Future research directions for
NCGS

Current research is focusing on non-GI symptoms reported to improve with
the GFD and continues to investigate the effects of gluten on intestinal
inflammation, permeability, and other pathways of both innate and adaptive
immunity in patients who do not have coeliac disease.

How common NCGS is, how it can be reliably identified and what its
underlying mechanisms are, warrant further evaluation. Without convincing
results showing effects on inflammatory or immune markers, NCGS should be
regarded as a sub-group of IBS and distinct from coeliac disease.

Concluding comments

We have some evidence for the
existence of NCGS, but this group remains poorly understood. We have no evidence
to allow a plausible explanation of the pathogenesis of NCGS and more definitive
research is needed to fulfill our understanding. Although the use of dietary gluten restriction in the management
of patients with functional gut symptoms may benefit a small number of people, lowering the dietary intake of FODMAPs
continues to be the first line therapy for IBS. Conducting
well-controlled dietary studies are complex; the most valid study design of
verifying the existence of NCGS remains unsubstantiated. Public health agencies
and the food industry must not perpetuate public demand and consumer trends for
the GFD without sufficient evidence first supporting the existence of NCGS.

Identifying patients with NCGS

Medical advice and dietetic supervision (ideally someone trained in the
low FODMAP dietary method) is imperative throughout this process.Key messages:

Self-reported NCGS and improved symptoms on a GFD may not be an accurate indication of the condition

Prevalence and diagnostic procedures including biomarkers are not yet clearly defined

Widespread promotion of GFD to treat gluten intolerance without first excluding coeliac disease may lead to coeliac disease not being detected and increase the risk of related consequences

Lowering the dietary intake of FODMAPs continues to be first line therapy for managing GI symptoms

Recommend referral of patients to a specialist dietitian

References

Vinning G, McMahon G. Gluten-free Grains: A demand-and-supply analysis of prospects for the Australian grains industry. Canberra, Australia: Rural Industries Research and Development Corporation, Australian Government, 2006

Rumessen JJ, and Gudmand-Hoyer, E. Fructans of chicory: intestinal transport and fermentation of different chain lengths and relation to fructose and sorbitol malabsorption. American Journal of Clinical Nutrition 1998;68:357-64.